This project is concerned with the metabolism of psychotomimetic 1-phenyl-2-aminopropanes with particular focus on 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Rabbit liver preparations are employed to examine the formation of specific metabolites which may be directly involved in covalent bond formation with biogenic amine receptor sites in the brain. The characterization of N-hydroxylation and O-demethylation metabolites has led to the hypothesis that the parent amine undergoes in vivo metabolic activation to molecules with alkylating potential. Stereochemical and kinetic studies are being pursued to evaluate this hypothesis. Extensive use of stable isotope dilution - Chemical ionization mass spectral analysis is made. Chemical model studies on the metabolic reactions of interest are also under investigation. BIBLIOGRAPHIC REFERENCES: Biomedical Application of Chemical Ionization Mass Spectrometry, the Stereoselective In Vitro Metabolism of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane. R. Weinkam, J. Gal, P. Callery and N. Castagnoli, Anal. Chem. 48, 203 (1976). Metabolic N-Demethylation of Nicotine Trapping of a Reactive Iminium Species with Cyanide Ion, T.-L. Nguyen, L.D. Gruenke and N. Castagnoli, J. Med. Chem., 19, 1168 (1976).